The protein of Wiskott β Aldrich Syndrome ( The Wiskott β Aldrich Syndrome Protein, WASp ) consists of 502 amino acid residues [1] and has a complex domain structure. It is expressed in hematopoietic cells and plays an important role in the reorganization of the cytoskeleton , signal transduction, and apoptosis [2] .
Wiscott β Aldrich Syndrome | |||||||||||||
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Symbol | ; IMD2; SCNX; THC; THC1; Wasp | ||||||||||||
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The WAS gene, mutations in which lead to the development of Wiskott-Aldrich syndrome , is located on the short arm of the X chromosome in the region of Xp11.4 - Xp11.21. More precisely, the WAS gene is located from48,683,789 to the 48,691,426th base pair on the X chromosome [3] . Mapping of the gene was carried out in 1994, it was found that the WAS gene consists of 12 exons and 11 introns [4] with a total length of approximately 1800 pairs of nucleotides [5] [6] .
At the C-terminus of the WASp protein, in the immediate vicinity of one another, the binding domains of monomeric actin and the Agr2 / 3 complex are located. This provides a spatial convergence of these molecules and facilitates the actin polymerization. At the N-terminus and in the central part of the protein, there are various regulatory domains (WH1, GBD, Polu-Pro site), which provide interconnection with many special protein molecules and phospholipids of the membranes. Thus, the WASp protein can serve as a mediator in the interaction of various specific factors with membrane structures and participate in the actin polymerization [7] [8] .
The occurrence of a mutation in the gene responsible for the synthesis of WASp protein leads to the appearance of a defective form of the protein or its complete absence, which entails the development of impaired immunity and hemostasis. At least 350 mutations are known [3] in the WAS gene, which are responsible for the development of X-linked Wiskott-Aldrich syndrome. Their main number falls on nucleotide substitutions (missense / nonsense mutations), splicing mutations and small deletions. Small insertions and large deletions are also detected [9] .
In patients with missense mutations , as a rule, there is a mild course of the disease, manifested mainly by thrombocytopenia. Patients with various deletions, nucleotide insertions, nonsense mutations, and splicing site mutations are characterized by more severe clinical manifestations [10] [11] .
Notes
- β P42768 [1-502], Wiskott-Aldrich syndrome protein, Homo sapiens
- β Wiskott-Aldrich Syndrome . Summary (Pdf) . orpha.net (2013) . The appeal date is January 7, 2017.
- β 1 2 A service of the US National Library of Medicine: Genetics Home Reference
- β WAS - Wiskott-Aldrich syndrome (eczema-thrombocytopenia) Archived February 1, 2014. , Resource of Asian Primary Immunodeficiency Diseases (RAPID)
- β Derry JM , Ochs HD , Francke U. Isolation of a novel gene mutated in Wiskott-Aldrich syndrome. (English) // Cell. - 1994. - Vol. 78, no. 4 - P. 635-644. - PMID 8069912 .
- β chrX: 48542185-48549817 7.633 bp. UCSC Genome Browser on Human Feb. 2009 (GRCh37 / hg19) Assembly
- β Gusev N. B. The movement of non-muscle cells and the reorganization of actin microfilaments // Soros Educational Journal. - 2001. - T. 7, No. 7. - S. 9-16.
- β Thrasher AJ , Burns S. Wiskott-Aldrich syndrome: a disorder of haematopoietic cytoskeletal regulation. (English) // Microscopy research and technique. - 1999. - Vol. 47, no. 2 - P. 107-113. - DOI : 10.1002 / (SICI) 1097-0029 (19991015) 47: 2 <107 :: AID-JEMT3> 3.0.CO; 2-H . - PMID 10523789 .
- β Database: HGMD - Human Gene Mutation Database.
- β Lemahieu V. , Gastier JM , Francke U. Novel mutations in the Wiskott-Aldrich syndrome protein gene and their effects on transcriptional, translational, and clinical phenotypes. (English) // Human mutation. - 1999. - Vol. 14, no. 1 . - P. 54-66. - DOI : 10.1002 / (SICI) 1098-1004 (1999) 14: 1 <54 :: AID-HUMU7> 3.0.CO; 2-E . - PMID 10447259 .
- β Lutskiy MI , Rosen FS , Remold-O'Donnell E. Genotype-proteotype linkage in the Wiskott-Aldrich syndrome. (English) // Journal of immunology (Baltimore, Md.: 1950). - 2005. - Vol. 175, no. 2 - P. 1329-1336. - PMID 16002738 .